Stewardship / Resistance Scan for May 04, 2022

News brief

Stewardship steps help Singapore hospital cut broad-spectrum antibiotics

A study conducted in a hospital with high rates of antibiotic resistance in Singapore found that sequential implementation of two antimicrobial stewardship interventions was associated with reduced use of broad-spectrum antibiotics, researchers reported yesterday in JAMA Network Open.

To examine the outcomes associated with the sequential implementation of prospective review and feedback (PRF) with computerized decision support systems (CDSS) at a university teaching hospital in Singapore, researchers conducted an interrupted time series analysis of antibiotic use, multidrug-resistant organism incidence, and other unintended outcomes at the hospital from 2007 through 2018.

Daily real-time PRF of piperacillin-tazobactam and carbapenems (intervention 1) was introduced at the hospital in 2009, and a CDDS that covered 52 infective syndromes and followed hospital empiric antibiotic guidelines (intervention 2) was introduced in 2011.

After implementation of intervention 1, the use of piperacillin-tazobactam and carbapenems increased at a slower trend of 0.33 (95% confidence interval [CI], 0.18 to 0.48) more defined daily doses (DDDs) per 1,000 patient-days per month, while use of other broad-spectrum antibiotics fell by –11.05 (95% CI, –15.55 to –6.55) fewer DDDs per 1,000 patient-days per month.

After intervention 2, there were −0.22 (95% CI, −0.33 to −0.10) fewer DDDs per 1,000 patient-days per month of piperacillin-tazobactam and carbapenems and −2.10 (95% CI, −3.13 to −1.07) fewer DDDs per 1,000 patient-days per month for other broad-spectrum antibiotics. Also after intervention 2, incidence of Clostridioides difficile decreased by –0.02 (95% CI, –0.03 to –0.01) cases per 1,000 patient-days per month.

The study also found that when compulsory use of CDDS for piperacillin-tazobactam and carbapenems was lifted in half of the hospital wards in March 2017 (intervention 3), use of the two antibiotics increased by 0.28 (95% CI, 0.02 to 0.55) DDDs per 1,000 patient-days per month.

"This cohort study found that implementation of PRF and CDSS was associated with limiting the use of piperacillin-tazobactam and carbapenems while reducing use of other broad-spectrum antibiotics in a hospital with high antibiotic resistance rates," the study authors wrote. "The continued use of CDSS was needed to sustain the decrease in use of piperacillin-tazobactam and carbapenem."
May 3 JAMA Netw Open study

Approval of tebipenem HBr in doubt, Spero says

Biopharmaceutical company Spero Therapeutics announced yesterday that it will immediately defer current commercialization activities for tebipenem pivoxil hydrobromide (HBr), an oral carbapenem currently under review by the Food and Drug Administration (FDA), after the agency cast doubt on approval of the drug.

The FDA has been reviewing Spero's New Drug Application (NDA) for tebipenem HBr for the treatment of complicated urinary tract infections (cUTIs) caused by certain microorganisms in patients with limited treatment options, with an approval decision initially expected in late June. The application included data from a phase 3 trial that found that 7 to 10 days of tebipenem HBr was non-inferior to 7 to 10 days of intravenous (IV) ertapenem, with a similar safety profile.

But in a press release, Spero said that the FDA informed company officials in a recent meeting that a new analysis of the trial's microbiological intention-to-treat population found that pre-specified non-inferiority margin of –12.5% was not met, and that the data in the review package "may be insufficient to support approval during this review cycle."

"We are disappointed that the FDA has identified substantive review issues, and we strongly believe that tebipenem HBr would offer healthcare providers, payers and patients an important oral antibiotic alternative to IV treatment for cUTI for patients with limited oral treatment options," said Spero CEO Ankit Mahadevia, MD.

The company said it will continue to work with the FDA on a path forward for tebipenem HBr, but will "immediately refrain from investment in near-term commercialization activities."

Spero also announced it will reduce its workforce by 75% and restructure operations to reduce costs.
May 3 Spero Therapeutics press release

News Scan for May 04, 2022

News brief

Neurologic illness may affect 1 in 8 hospitalized COVID-19 patients

Nearly 13% of hospitalized COVID-19 patients had serious neurologic illnesses in the first year of the pandemic, suggests an international study published last week in Critical Care Explorations.

The observational study, led by Boston University researchers, analyzed data from 179 hospitals in 24 countries participating in the Society of Critical Care Medicine's COVID-19 registry from Mar 25, 2020, to Mar 9, 2021.

Among the 16,225 patients enrolled in the registry whose hospital release status was available, 12.9% had serious neurologic illnesses, of whom 10.2% had encephalopathy (disease affecting brain structure or function) at admission, 2.0% had a stroke, 1.5% had seizures, and 0.5% had encephalopathy or meningitis (inflammation of the membranes surrounding the brain and spinal cord) at admission or during their hospital stay.

Patients with these illnesses were older than those without (median, 72 vs 61 years) and had a higher prevalence of underlying conditions, including serious vascular risk factors and a history of stroke or neurologic disorders. After adjustment for age, sex, and time since the pandemic began, serious neurologic illnesses were tied to more severe disease (odds ratio [OR], 1.49).

COVID-19 patients with neurologic illnesses were more likely to be admitted to an intensive care unit (ICU) (OR, 1.45) and need extracorporeal membrane oxygenation (OR, 1.78) and dialysis (OR, 1.99).

Odds of hospitalization, ICU stay, and death by 28 days were higher among patients with neurologic manifestations (OR, 1.51, 1.37, and 1.58, respectively). They also had fewer days out of the hospital and ICU and off a ventilator (estimated difference, -0.84, -1.34, and -0.84 days, respectively). Relative to their White peers, Black patients had more strokes, seizures, and encephalopathy.

"Our findings show that encephalopathy at hospital admission is present in at least one in 10 patients with SARS-CoV-2 infection, while stroke, seizures and meningitis/encephalitis were much less common at admission or during hospitalization," lead author Anna Cervantes-Arslanian, MD, said in a Boston University news release.
Apr 25 Crit Care Explor study
May 4 Boston University news release

Study suggests double-masking for COVID-19 hurts more than helps

A study yesterday in Physics of Fluid shows that wearing two face coverings to protect against COVID-19 does not offer more respiratory protection, and may offer a false sense of protection for the wearer.

Researchers from Florida State University and Johns Hopkins University used fluid dynamics simulation models to show how improperly fitted masks—even when layered—force flow from a simulated cough out of the perimeter gaps (sides, top, and bottom) of masks.

They ran the simulation of a cough jet with a peak velocity of 10 meters per second on 100 adult male and 100 female head shapes to account for the natural differences in face shape and symmetry.

With different noses, chins, and cheekbones, perimeters changed for facial coverings.

"Facial asymmetry is almost imperceivable to the eye but is made obvious by the cough flow through the mask," said co-author Tomas Solano, PhD, from Florida State University in a press release from the American Institute of Physics (AIP), which publishes the journal.

Through multiple tests, the authors found masks that were less porous forced particles to travel through gaps, while more-porous masks allowed particles to stream directly out of the mask. In double-masking, the increased porosity led to more perimeter leakage.

"We found that the flow through the mask increases with an increase in mask porosity. On the other hand, the gap leakage is inversely proportional to the mask's porosity," the authors wrote.
May 3 Phys Fluids study
May 3 AIP press release

High-path avian flu strikes more flocks in 6 states

Six states, mostly in the Midwest, reported more highly pathogenic avian flu outbreaks in poultry flocks, according to official reports from federal and state agriculture officials.

Minnesota reported two more outbreaks, one at a commercial turkey farm in in Lyon County in the southwest part of the state, and another at a backyard location in Chisago County near the Twin Cities. Minnesota has now reported 68 outbreaks, which have led to the loss of more than 2.7 million birds, according to the Minnesota Board of Animal Health (MBAH).

Illinois reported its third outbreak, according to the US Department of Agriculture (USDA) Animal and Plant Health Inspection Service (APHIS). The outbreak occurred in Kane County, just west of Chicago. The Illinois Department of Agriculture (IDOA) said the event involved backyard birds. Iowa also reported an outbreak in backyard birds, raising its overall total to 19, according to the Iowa Department of Agriculture and Land Stewardship (IDALS).

Elsewhere in the Midwest, South Dakota reported its 37th outbreak, which involved a commercial turkey farm in Beadle County in the east central region. Wisconsin reported 5 new outbreaks, including 2 at commercial turkey farms housing 66,500 birds in Barron County in the west central part of the state. The others occurred in backyard birds in Barron, Polk, and Sauk counties, bringing the state's total to 16 outbreaks.

In the northeast, Pennsylvania reported two outbreaks at commercial duck farms in Berks County in the southeast, lifting its total to nine. One struck a breeder farm, and the other occurred at a meat producer.

The outbreaks in the six states are part of ongoing activity involving the Eurasian H5N1 strain, which has fueled outbreaks in 32 states and led to the loss of 36.8 million birds.
MBAH avian flu update page
APHIS poultry outbreak updates
IDOA avian flu update page
May 3 IDALS press release